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PubMed2001

Single site polymorphisms and alternative splicing of the human CD13 gene--different splicing frequencies among patients with acute myeloid leukaemia and healthy individuals.

Within the haematopoietic system, CD13/aminopeptidase N (APN), a transmembrane glycoprotein, is expressed on the surface of early committed progenitors of granulocytes and monocytes and by all cells of these lineages as they mature. CD13 is expressed on the majority of leukaemic myeloblasts in acute myeloid leukaemia (AML), and on leukaemic lymphoblasts in a small percentage of acute lymphoid leukaemia cases. Thus, anti-CD13 monoclonal antibodies are used as diagnostic markers in leukaemia typing. By systematically amplifying overlapping reverse transcription polymerase chain reaction (RT-PCR) amplicons throughout the CD13 mRNA, we identified two splice variants in which exon 3 and exon 14 were lost. Fourteen healthy individuals and 34 patients with AML were screened for these splice variants. All healthy individuals, and the majority of AML patients, had both splice variants but they represented less than 10% of the total RT-PCR-amplified CD13 product. Increased expression of both truncated CD13 mRNA forms were observed in 6% of AML patients, whereas no detectable exon 3 or exon 14 splice variants could be generated in 26% and 9% of AML patients respectively. The different splicing frequencies may reflect altered processing of pre-mRNA or expansion of certain cell types for some AML patients, even though no correlation existed to blast percentage, FAB classification, surface antigens or cytogenetic characteristics. In addition, we identified an intron of 506 bp between exon 1 and exon 2 as well as two sites of single nucleotide polymorphism with a heterozygosity index of about 0.5, making them useful as genetic markers.

Acute Disease↗

PubMed2005

Genetic classification of benign and malignant thyroid follicular neoplasia based on a three-gene combination.

Thyroid carcinoma is a common endocrine cancer with a favorable prognosis if subjected to timely treatment. However, the clinical identification of follicular thyroid carcinoma (FTC) among patients with benign thyroid nodules is still a challenge. Preoperative fine needle aspiration-based cytology cannot always differentiate follicular carcinomas from benign follicular neoplasias. Because current methods fail to improve preoperative diagnosis of thyroid nodules, new molecular-based diagnoses should be explored. We conducted a microarray-based study to reveal the genetic profiles unique to FTC and follicular adenomas (FAs), to identify the most parsimonious number of genes that could accurately differentiate between benign and malignant follicular thyroid neoplasia. We confirmed our data by quantitative RT-PCR and immunohistochemistry in two independent validation sets with a total of 114 samples. We were able to identify three genes, cyclin D2 (CCND2), protein convertase 2 (PCSK2), and prostate differentiation factor (PLAB), that allow the accurate molecular classification of FTC and FA. Two independent validation sets revealed that the combination of these three genes could differentiate FTC from FA with a sensitivity of 100%, specificity of 94.7%, and accuracy of 96.7%. In addition, our model allowed the identification of follicular variants of papillary thyroid carcinoma with an accuracy of 85.7%. Three-gene profiling of thyroid nodules can accurately predict the diagnosis of FTC and FA with high sensitivity and specificity, thus identifying promising targets for further investigation to ultimately improve preoperative diagnosis.

Adenocarcinoma, Follicular↗

PubMed1997

Recurrent aphthous stomatitis in the diagnosis of Behçet's disease.

Recurrent aphthous stomatits (RAS) is also known as recurrent oral ulcers, recurrent aphthous ulcers, or simple or complex aphthosis. RAS is the most common inflammatory ulcerative condition of the oral mucosa in North American patients. RAS has been the subject of active investigation along multiple lines of research including epidemiology, immunology, clinical correlations and therapy. Clinical evaluation of the patient requires correct diagnosis of RAS and classification of the disease based on morphology (MIAU, MJAU, HU) and severity (simple versus complex). In order to properly diagnose and treat a patient with lesions of RAS, the clinician must exclude other causes of acute oral ulcers. Complex aphthosis and complex aphthosis variants associated with systemic disorders should be considered. The aphthous-like oral ulcerations of patients with HIV disease represent a challenging differential diagnosis. The association of lesions of RAS with hematinic deficiencies and gastrointestinal diseases provides an opportunity to identify a "correctable cause" which, with appropriate treatment, can result in a remission or substantial lessening of disease activity. Finally, when all of these factors are considered, the evaluation of the patient for Behçet's disease can be continued on firm grounds that one of the major criteria for the diagnosis of Behçet's disease has been met.

Behcet Syndrome↗

PubMed2002

[Characterization of renal masses].

The characterization of renal masses relies mainly on CT which remains the gold standard in the diagnosis of renal tumors and cysts. Ultrasound enables to diagnose benign cysts which account for the majority of incidentally detected renal masses. MR imaging is useful in the diagnosis of renal masses that remain indeterminate at CT. Moreover, it is efficient as a substitute when CT is contraindicated. Renal masses include three categories with respect to the size and the gross architecture of the lesion: indeterminate very small masses (less than 10mm in diameter); cystic renal masses and solid renal masses that exhibit postcontrast tumor tissue enhancement. Characterization of cystic renal masses relies mainly on the Bosniak classification which consists of four categories: benign simple cysts (cat I); minimally complicated cysts (cat II); indeterminate cystic renal masses that include cystic renal tumors (multiloculated or not) and complex cysts; cystic renal cell carcinomas (cat IV). Solid renal masses include pseudotumors (normal variants, renal dysmorphisms and inflammatory renal masses) and renal neoplasms among which CT enable to distinct: typical large renal cell carcinomas, typical fat-containing angiomyolipomas and indeterminate renal tumors.

Adult↗

PubMedDate not supplied

Towards the identification of (a) gene(s) for autosomal dominant medullary cystic kidney disease.

Medullary cystic kidney disease (MCKD) belongs with nephronophthisis (NPH) in a group of inherited tubulo-interstitial nephritis, which has been referred to as the NPH-MCKD complex. Although MCKD and NPH share morphological features, they differ in several respects. The most common variant is recessive juvenile NPH, with onset in childhood and leading to end-stage renal disease (ESRD) within the 2nd decade of life; the most frequent extrarenal involvement is tapeto-retinal degeneration. MCKD is a dominant condition recognized in later life and leading to ESRD at the age of 50 years; hyperuricemia and gout can be associated features. The first sign of MCKD is polyuria; later, the clinical findings relate to renal insufficiency. Originally, NPH and MCKD were considered separate entities. Subsequently, it has been suggested that the two diseases were a single disorder due to the clinico-pathological identity. This unifying conception was later refuted due to the identification of MCKD dominant families. Recently, considerable insight has been gained into the genetics of the NPH-MCKD complex. The majority of juvenile NPH cases are due to deletion of the NPHP1 gene on chromosome 2q13. Genes for infantile and adolescent NPH have been localized respectively to chromosome 9q22-q31 and 3q22. A new locus, NPHP4, has been recently identified on chromosome 1p36. Two genes predisposing to dominant MCKD, MCKD1 and MCKD2, have been localized to chromosome 1q21 and 16p12. Independent confirmation of the locations of MCKD1 and MCKD2 in other MCKD families, with or without hyperuricemia and gout, has been reported. The gene for familial juvenile hyperuricemic nephropathy (FJHN), a phenotype that is very similar to MCKD, was recently mapped to 16p12, in a region overlapping with the MCKD2 locus, raising the question as to whether MCKD2 and FJHN are allelic variants of the same disease entity. The ultimate proof of the allelism between MCKD2 and FJHN will be provided by the identification of the responsible gene(s). Identification and characterization of the MCKD and FJHN genes will help to clarify the pathogenesis and classification of hereditary tubulo-interstitial nephritides.

Humans↗

PubMed2003

Peripheral T-cell lymphomas: clinical features and prognostic factors of 92 cases defined by the revised European American lymphoma classification.

The purpose of this study was to better define the clinical features and natural history of peripheral T-cell lymphomas (PTCL) entities included in the Revised European American lymphoma (REAL) classification. Cases of PTCL were retrieved from the records of the Department of Pathology and classified according to the REAL classification. In addition, cases of anaplastic large cell lymphoma (ALCL) were divided into classical, small cell, and primary cutaneous subtypes, and immunostaining for the anaplastic large-cell kinase (ALK) protein was performed on all cases of ALCL. Clinical features, response to therapy and survival were abstracted. Ninety-two cases of PTCL with adequate clinical information were retrieved. There were 40 cases of ALCL (30 classical, 7 small cell variant, 3 primary cutaneous), 28 PTCL, unspecified, 13 angioimmunoblastic T-cell lymphoma and 11 with other entities. The patients had a median age of 48 years with a range of 6-84 and had an estimated overall survival (OS) of 49% and progression-free survival (PFS) of 22% at 5 years. The International Prognostic Index (IPI) was a significant prognostic factor for both progression-free and OS. Histology was a significant predictor of PFS with anaplastic large cell having the best prognosis. ALK expression was not associated with an improved progression-free or overall-survival in patients with systemic T-cell ALCL. In conclusion, the REAL classification describes distinct PTCL entities. The IPI is the most important predictor of progression-free and OS in patients with PTCL. ALK expression may not provide prognostic information for systemic ALCL.

Adolescent↗

PubMed2005

Anatomical and physiological classification of hepatic vein dominance applied to liver transplantation.

BACKGROUND: Proper outflow reconstruction is essential in LDLT. Preoperative planning requires meticulous attention to hepatic vein dominance patterns. The purpose of our study was to provide a combined anatomical-physiological classification of hepatic vein dominance useful for surgical decision-making in both donors and recipients. METHODOLOGY: We analyzed 3-dimensional CT-imaging reconstructions of 55 potential live liver donors evaluated at our Institution between January 2003 and May 2004. RESULTS: Our data revealed that: 1) The middle hepatic vein (MHV) and left hepatic vein (LHV) show a relative lack of anatomical diversity, whereas the right hepatic vein (RHV) exhibits multiple variants, 2) 45% donors had inferior hepatic veins (IHV) with anatomically and physiologically relevant venous drainage territories, 3) The RHV is usually dominant when present as a single vein without anatomical IHV (type 1A), or when considered as a complex with IHV (type 1Bx) (80% vs. 88%), 4) Only 55% of dominant type 1Bx RHV/IHV-complex automatically included a dominant type 1By RHV by itself, 5) A single RHV out of anatomical complex with IHV (type 1By) was dominant in only 48% of our donor candidates, 6) The MHV types 2A and 2By are strongly dominant accounting for up to 57% of total liver volume (TLV). CONCLUSIONS: We propose a new classification based on both anatomical and physiological hepatic venous configurations. Our model also provides a new nomenclature that can be universally applied to preoperative planning in LDLT.

Adolescent↗

PubMed2026

XXYLT1 and Mendelian Retinal Dystrophy.

IMPORTANCE: Substantial unexplained heritability remains for pathogenic inherited retinal disease (IRD) variants. Application of genome-wide association studies (GWAS) could help identify causal genes in rare diseases. OBJECTIVE: To leverage a GWAS for the discovery of IRD-associated genes. DESIGN, SETTING, AND PARTICIPANTS: This GWAS analysis was combined with replication of findings in 2 independent IRD cohorts. The study was conducted from January 2024 to December 2025 in a multicenter setting through FinnGen, 100 000 Genomes Project, and the National Health Service Genomic Medicine Service combined with clinical cohort from the Oulu University Hospital. Using IRD criteria from the International Classification of Diseases, 9th and 10th Revisions, 540 individuals with IRD and 473 945 control individuals were identified in the FinnGen study. For validation of FinnGen results, 49 patients were recruited from Oulu University Hospital. Results were further validated in 2 individuals identified from the UK cohort. MAIN OUTCOMES AND MEASURES: The GWAS and proteomics analysis were performed in the FinnGen cohort. Sanger and whole-genome sequencing and RNA approaches were used in a clinical IRD cohort to validate pathogenicity of the identified XXYLT1 variant. RESULTS: This GWAS identified 13 recessive loci reaching genome-wide significance (defined as P < 5 × 10-8). Of these, 4 (near or within XXYLT1, ANKRD10, DYM, and CBLN4) had not been associated with IRD, including the XXYLT1 c.505-1G>C founder variant. This variant was further genotyped in the clinical replication cohort, leading to identification of 5 more homozygous individuals from 4 families. The phenotype was consistent with a cone-rod or macular dystrophy, with visual deterioration, cystoid macular edema and/or schisislike macular abnormalities. The effect of the XXYLT1 c.505-1G>C variant was further investigated using RNA sequencing and complementary DNA amplicon sequencing, demonstrating exon 2 skipping and a loss-of-function effect. These findings were replicated in an independent population identifying 2 patients from the UK harboring a homozygous XXYLT1 c.766G>A, p.(Glu256Lys) missense variant. CONCLUSIONS AND RELEVANCE: This GWAS identified an association between XXYLT1 and IRD. These results affirm that GWAS in a founder population can be used as a potential tool for the discovery of rare mendelian disease genes and that XXYLT1 should be considered in clinical IRD gene panels.

Humans↗

PubMed1995

Lipomatous tumours of soft tissues: an update.

This review summarizes the clinicopathological features of recently characterized variants of lipomatous tumours of soft tissue, attempts to deal with some difficult conceptual issues relating to adipocytic neoplasms and aims to provide an update on cytogenetic aspects of fatty tumours. Myolipoma is a rare benign neoplasm, occurring most frequently in adults in the deep soft tissue of the abdomen or retroperitoneum, and is composed of irregularly admixed mature adipose and smooth muscle tissues. Chondroid lipoma represents an unusual benign lesion occurring mainly in adult females subcutaneously or in deep soft tissue; it is easily mistaken for myxoid liposarcoma or extraskeletal myxoid chondrosarcoma. Spindle-cell liposarcoma is a variant of well-differentiated liposarcoma quite commonly found in subcutaneous tissue of the shoulder region and upper limbs and is composed of relatively bland-appearing spindle cells mixed with a well-differentiated liposarcomatous component. Recently there has been considerable debate about classification of lipomatous tumours. The term atypical lipoma was proposed for a group of well-differentiated non-metastasizing liposarcomas arising in surgically amenable soft tissues and for deep-seated atypical adipocytic neoplasms that show variation in adipocytic size and atypical stromal cells but lack lipoblasts. However, these neoplasms recur repeatedly and may dedifferentiate and thereby acquire metastatic potential. We use the diagnosis atypical lipoma with caution and propose to use the terms well-differentiated liposarcoma and atypical lipoma interchangeably. The relationship between myxoid and round-cell liposarcoma, which constitutes the morphological spectrum of a single entity, has been clarified but there remain considerable problems in defining likely clinical behaviour. The recent advances in cytogenetic characterization and classification of lipomatous tumours, which is already proving to be of diagnostic importance, are reviewed, and the genetic importance of the distinct chromosomal translocation in myxoid/round cell liposarcoma is briefly discussed.

Adult↗

PubMed2004

Evaluation of various species demarcation criteria in attempts to classify ten new tombusvirus isolates.

The usefulness of various suggested species demarcation criteria was compared in attempts to determine the taxonomic status of ten new tombusvirus isolates. Five of them (Lim 1, 2, 3, 5 and 6) were obtained from different sources of commercially grown statice (Limonium sinuatum), two (Gyp 1 and 2) from different sources of commercially grown Gypsophila paniculata and three from water samples, i.e. from a small river (Schunter) in Northern Germany, from a brook (near Dossenheim) in Southern Germany and from the groundwater in a Limonium production glasshouse in the Netherlands (Lim 4). The immunoelectron microscopical decoration test allowed a quick preliminary assignment of various isolates to several known tombusviruses. A more precise analysis of the relationships was achieved by comparing the deduced amino acid sequences of the coat proteins. Sequence as well as serological data suggested that eight of the isolates should be classified as strains or variants of either Carnation Italian ringspot virus, Grapevine Algerian latent virus, Petunia asteroid mosaic virus or Sikte waterborne virus, respectively, whereas the 9th isolate (Lim 2) appears to represent a distinct new tombusvirus species. The case of the 10th isolate (Lim 5) illustrates the classification problems experienced when the properties of a virus place it close to the more or less arbitrary man-made borderline between virus species and virus strains. The coat protein gene sequences were also determined for some viruses for which these data had not yet been available, i.e. Neckar river virus, Sikte waterborne virus and Eggplant mottled crinkle virus. The sequences of the coat protein gene and also of ORF 1 of the latter virus proved to be almost identical to the corresponding genome regions of the recently described Pear latent virus, which for priority reasons should be renamed. Criteria which have been suggested in addition to serology and sequence comparisons for tombusvirus species demarcation, i.e. differences in natural and in experimental host ranges, in cytopathological features and in coat protein size, appear to be of little value for the classification of new tombusviruses.

Base Sequence↗

PubMed1984

8;21 translocation in acute granulocytic leukaemia: cytological, cytochemical and clinical features.

Thirty patients with the 8;21 translocation and three with closely related variants have been studied. Ages ranged from 3 to 64 years (mean 28.3). Thirty-one were entered into the MRC's 8th Acute Myeloid Leukaemia Trial. Twenty-nine (88%) achieved complete remission. Marrow smears from most patients showed granulocytic maturation (M2, FAB classification) with characteristic abnormalities, but at least six showed predominantly myeloblastic (M1) morphology. The blast cells were markedly heterogeneous with regard to size and nuclear cytoplasmic ratio. Typical staining patterns were observed in the blast cells using Sudan black B and diaminobenzidine peroxidase stains, and to a lesser extent with periodic acid-Schiff and chloroacetate esterase. Butyrate esterase was negative in all cases. Auer rods were present in the granulocyte precursors in 31 cases and in eosinophil precursors in two cases. In most cases the existence of the translocation was predicted from the cytological and cytochemical findings. Seven patients developed solid leukaemic deposits, principally in the mastoid cavities, orbital cavities or thoracic spine (extradural).

Adolescent↗

PubMed1999

[Intra-arterial regional perfusion in destructive forms of acute pancreatitis].

The results of using regional infusion therapy in 17 patients with destructive pancreatitis are analyzed which appeared to be more effective, than the systemic infusion of drugs in stopping the symptoms of endotoxicosis leveling the functional insufficiency of the liver and kidneys, disturbances in hemodynamics and hemostasis. The best results have been obtained when using a modified method of regional therapy (celiac-aortal dislocational regional infusion) in the complex treatment of destructive pancreatitis. This method has a number of advantages as compared with intra-aortic variant of regional therapy. Hospital lethality in the process of using the methods of regional therapy in the complex treatment of destructive pancreatitis was 17.5%. In the control group of patients treated without regional infusion lethality was within the limits of 28%. A modified classification of endotoxicosis according to the degree of the disease is proposed. In order to estimate the severity of the syndrome of intoxication and effectiveness of the given therapy principally new integrative parameters of clinical and laboratory research are used.

Acute Disease↗

PubMed1981

[Morphological typing of respiratory tract tumors].

A group of 224 tumours of the respiratory tract was used to present experience with the standard histological classification, as proposed by WHO--incl. the revised version of pulmonary tumour classification which is under preparation. Electron microscopic facts from the authors' own material as well as from recent literature served in particular as a stimulus for the critical evaluation of some details of the standard classification. It served also as the basis for recommendations for rational modifications for its use in particular in Czech and Slovak speaking areas: 1. Prefer in respiratory pathways the term papilloma from respiratory epithelium to "transient" papilloma and not differentiate exophytic and inverted forms. 2. Respect the differentiation of bronchial adenomas and carcinoids, but identify atypical carcinoids with small-cell (oat-cell) carcinomas. 3. As to other carcinomas of the respiratory pathways to differentiate only between squamous carcinomas (spindle-cell and verrucal), glandular (in addition to adenoid cystic and mucoepidermoid) and undifferentiated. 4. In the section of pulmonary carcinomas to abandon completely large-cell carcinomas and to describe tumours which cannot be included in other groups as undifferentiated carcinomas. 5. Avoid in the other respect satisfactory classification pattern of pulmonary carcinomas subvariants (in particular in the group of glandular carcinomas) and include exceptional units in the group "others". 6. Arrange the group of malignant lymphomas according to the extrapulmonary classification pattern and include there from the group of tumourous lesions so-called lymphoproliferative processes, eosinophil granuloma and gangrenescent granuloma. 7. Use consistent with the nomenclature in the sphere of the nervous system the term olfactory neuroblastoma and omit its rare sub-variants.

Humans↗

PubMed1996

An ontological perspective on surgical procedures.

We studied terminological phrases on surgical procedures-from coding systems, controlled vocabularies, textbooks, and medical records-by an ontological point of view. A surgical procedure can be accurately described only by a set of sentences, in textbooks or surgical reports; a terminological phrase is just a short synthesis of that description. We outline three points of view actually used to construct a phrase, based on i) relevant phases and variants; ii) focus on structures, functions and pathologies; iii) evolution of information and decisions during the process of care. For each of them we discuss potential principles and mechanisms, with the aim of deriving guidelines to generate homogeneous systematic names, to organize regularities in classifications and nomenclatures, to normalize expressions in formal languages.

Medical Informatics Computing↗

PubMed2001

Appropriate laboratory assessment as a critical facet in the proper diagnosis and classification of von Willebrand disorder.

The correct diagnosis and classification of von Willebrand disease or disorder (VWD) is crucial because the presenting biological activity of von Willebrand factor (VWF) determines both the haemorrhagic risk and the subsequent clinical management. A variety of laboratory assays may be employed, not necessarily restricted to assessments of VWF. Because of assay limitations and von Willebrand disease heterogeneity, no single test procedure is sufficiently 'robust' to permit the detection of all VWD variants. Classically, the test panel might include any combination of: (a) skin bleeding time, (b) von Willebrand factor antigen assay, (c) factor VIII C level, (d) assessment of 'functional' von Willebrand factor (collagen-binding activity or ristocetin co-factor assay), (e) ristocetin-induced platelet aggregation, and (f) multimer analysis. There have also been many new diagnostic developments that have begun to influence the diagnostic process. These include the automation of existing assay procedures, new automated platelet function analyzers such as the PFA-100, and specific von Willebrand factor-factor VIII-binding assays. This chapter focuses on the recommended laboratory process for the investigation of VWD. The selection of an appropriate combination test panel and testing sequence is crucial for the proper diagnosis and classification of congenital von Willebrand disease.

Clinical Laboratory Techniques↗

PubMed2000

Analysis of the actinobacterial insertion in domain III of the 23S rRNA gene of uncultured variants of the bacterium associated with Whipple's disease using broad-range and 'Tropheryma whippelii'-specific PCR.

Heterogeneity in the 16S-23S rDNA spacer of uncultured 'Tropheryma whippelii' has previously been reported. In this study, the hypervariable insertion in the 23S rDNA domain III characteristic for actinobacteria was analysed. The finding of a unique sequence virtually identical among the subtypes supports the classification of 'T. whippelii' among the actinobacteria and the concept of three subtypes rather than three subspecies, and provides an alternative target for diagnostic assays.

Actinobacteria↗

PubMed2001

[Erysipelas. Clinicopathological classification and terminology].

Erysipelas and necrotizing fasciitis are the words used to qualify 2 well-defined aspects of acute microbial dermohypodermal infection. According to the literature a third word, "cellulitis" is used to describe a large variety of inflammatory conditions of soft tissues, either infectious or not. The authors who advocate using this word consider either that an infectious cellulitis is a clinical variant differing from erysipelas or fasciitis, or that it describes the whole spectrum of acute microbial infections of soft tissues, including these 2 entities. This term, whatever its meaning, has no anatomical or histopathological validation. It should be definitively deleted and replaced by "dermohypodermal infection".

Erysipelas↗

PubMed2000

Amidocarbonylation-An Efficient Route to Amino Acid Derivatives.

Atom efficient, multicomponent reactions that lead to high-value products from inexpensive starting materials are of both economic and ecological interest for industrial organic synthesis. alpha-Amino acids are amongst the most important compounds in chemistry and biology. As well as their biochemical significance as building blocks of peptides and proteins, alpha-amino acids are also becoming increasingly interesting as fine chemicals. Possibly one of the key reactions in the preparation of these compounds is transition metal catalyzed amidocarbonylation, where the alpha-amino acid framework is constructed in a single step from an aldehyde, an amide, and carbon monoxide. This article gives a current overview of transition metal catalyzed amidocarbonylation reactions used in the synthesis of alpha-amino acids derivatives. A classification and summary of the significant features of this three component reaction is first presented together, with an historical introduction. This section is followed by two sections on cobalt- and palladium-catalyzed amidocarbonylation. A discussion of the mechanism of each of the different amidocarbonylation variants form an introduction. Overviews on further synthetic development of the methodology, such as the domino reaction with an amidocarbonylation step and the expansion of the range of starting materials, form the main topics of both variants. The potential of the method is demonstrated with the help of examples of special synthetic utility (for example, the preparation of arylglycines). Finally, possibilities for future developments in transition metal catalyzed amidocarbonylation reactions are proposed on the basis of the current state of knowledge.

Journal Article↗